Magnetic Resonance Spectroscopy (MRS) is an analytical method that may be used to identify and quantify certain metabolites in samples or areas of interest in the body. While relying on similar principles and using similar equipment, MRS differs from conventional Magnetic Resonance Imaging (MRI) in that the obtained spectra provide physiological and chemical information about the atoms and molecules in the sample, instead of anatomy and positional information used to form an image. By exploiting the magnetic properties of certain atomic nuclei, MRS can provide detailed information about the structure, dynamics, reaction state, and chemical environment of atoms or the molecules in which they are contained. Similar to MRI, MRS is typically performed by placing the subject or object to be imaged at or near the isocenter of a strong, uniform magnetic field, B0, known as the main magnetic field. The main magnetic field causes the atomic nuclei (spins) that possess a magnetic moment in the matter comprising the subject or object to become aligned in the magnetic field. The spins form a magnetization that precesses around the magnetic field direction at a rate proportional to the magnetic field strength.
If the magnetization is perturbed by a small radio-frequency magnetic field, known as B1 magnetic field, the spins may emit radio frequency (RF) radiation at a characteristic frequency. By applying the B1 magnetic field as one or more timed pulses and/or sequences of pulses with delay periods in between them, the emitted RF radiation can be detected and analyzed to yield information that may be used to identify and quantify chemical compounds within an object and infer information about metabolic activity. Various techniques utilizing specific sequences of RF pulses, having specific timing, frequencies, and intensities, have been developed, providing new advances, as well as introducing new challenges.
MRS experiments may gather data in one dimension (1D MRS) or two dimensions (2D MRS). Spectra obtained in 1D-MRS relate to the chemical shift properties of the nuclei in the sample. J-resolved spectroscopy—one form of 2D MRS—may be used to analyze molecules for which the 1D-MRS spectra contain overlapping spectral peaks (multiplets) due to J-coupling. J-coupling arises from the interaction of different spin states through the chemical bonds of a molecule and may provide insight into the connectivity of atoms in a molecule. The J-resolved spectrum vertically displaces the multiplet from each nucleus by a different amount. Each peak in the 2D spectrum will have the same horizontal coordinate that it has in a non-decoupled 1D spectrum, but its vertical coordinate will be the chemical shift of the single peak that the nucleus has in a decoupled 1D spectrum.
One challenge in the field of MRS has arisen due to the use of a relatively high magnitude main magnetic field. While in conventional MRI the main magnetic field strengths range from 0.2 to 3 T, MRS may employ a main magnetic field of 1.5 T or more. Higher field strengths have the advantage of higher signal-to-noise ratio (SNR), better resolution and shorter acquisition times (1,2). However, the separation (or dispersion) of MRS spectra is magnetic field dependent and the increased chemical shift dispersion sets higher demand on the bandwidth (BW) of radiofrequency (RF) pulses that are used for the localization in MRS. Chemical shift displacement error (CSDE) is proportional to the amplitude of static field (B0) and reversely proportional to the BW of slice-selective RF pulses (1,3-5).
Point-resolved spectroscopy (PRESS) is one pulse sequence commonly used in MRS. In the conventional PRESS sequence, the MR spectrum is acquired using one 90° pulse followed by two 180° pulses. The first 180° pulse is applied after a time TE1/2 from the first (90°) pulse, with the second 180° pulse being applied after a time TE1/2+TE/2 from the first (90°) pulse. A MR signal is acquired after a time TE. Because two slice-selective 180° refocusing pulses are used in conventional PRESS, the chemical shift artifact is especially severe (6). The limited BWs may not only cause CSDEs but may also lead to spatially dependent evolution of J-coupling, which may result in additional J-refocused artifactual peaks in two-dimensional (2D) J-resolved spectroscopy (JPRESS) (7-9). For a pair of coupled spins with a large chemical shift difference, one spin may not undergo the 1800 refocusing pulses due to the finite BW of the RF pulses in the voxel selected for its J-coupled partner. Therefore J-coupling will be refocused instead of evolving during the echo time (TE), which leads to additional so-called J-refocused peaks. The intensities of the intended J-resolved peaks may be reduced, thereby impairing spectral quantification.
RF field (B1) inhomogeneity also presents issues in MRS. At high magnetic field strengths, conventional RF pulses cannot provide uniform flip angles of the magnetization in the presence of nonuniform B1. Deviations from the intended flip angles may not only lead to signal attenuation and additional unwanted signals (thus compromising the reliability of the experiments), but may also increase the sidelobes of the slice profile, leading to unwanted non-zero flip angles outside the region of interest (ROI) (10). In 1H MRS experiments on the brain, accurate volume selection using slice-selective RF pulses may prevent contamination of a large lipid signal from scalp or water signal from poorly shimmed regions outside the selected volume (11).
One approach that has been successful in solving or mitigating the above issues is to use adiabatic RF pulses (2,3,12-21). Adiabatic pulses offer large BWs and produce a uniform flip angle despite variation in B1, provided that the B1 field strength is above a certain threshold. However, in contrast to conventional RF pulses which can rotate magnetization around an axis in the rotating frame, single adiabatic pulse cannot generate plane rotation (5,18). If a pair of adiabatic refocusing pulses are used, the second adiabatic refocusing pulse can compensate or cancel the phase dispersion generated by the first adiabatic refocusing pulse. Therefore, a pair adiabatic refocusing pulses is usually applied to define a slice. A single shot spin-echo based sequence called LASER, which stands for “localization by adiabatic selective refocusing,” has been used for 1D MRS (18). LASER uses a non-slice-selective excitation pulse followed by three pairs of adiabatic full-passage (AFP) pulses for signal refocusing as well as selection of three orthogonal slices in space. LASER, however, is only a 1D MRS technique and cannot provide information on J-coupling.
Recently, adiabatic pulses were employed in 1D localized MRS, spectral editing, total correlation spectroscopy, and localized chemical shift correlated spectroscopy, etc. (1,4,22-24). However, the most commonly used localized 2D J-resolved spectroscopy, i.e., JPRESS, is still based on the PRESS sequence. As described above, PRESS suffers from several drawbacks. Namely, PRESS exhibits increased chemical shift displacement error, spatially dependent J-coupling evolution resulting in additional J-refocused peaks, and sensitivity to RF field inhomogeneity leading to signal attenuation and unwanted signals. These drawbacks can lead to reduced intensities of the desired J-resolved peaks, impair spectral quantification, increase sidelobes of the slice profile and compromise the overall reliability of spectral quantification. Thus, a need remains in the art for an improved 2D J-resolved spectroscopy technique that provides for more reliable and accurate quantification of metabolites at 3 T and higher field strengths.